Obesity-induced secretory disorder of adipose tissue–derived factors is important for cardiac damage. However, whether platelet-derived growth factor-D (PDGF-D), a newly identified adipokine, regulates cardiac remodeling in angiotensin II (AngII)–infused obese mice is unclear. Here, we found obesity induced PDGF-D expression in adipose tissue as well as more severe cardiac remodeling compared with control lean mice after AngII infusion. Adipocyte-specific PDGF-D knockout attenuated hypertensive cardiac remodeling in obese mice. Consistently, adipocyte-specific PDGF-D overexpression transgenic mice (PA-Tg) showed exacerbated cardiac remodeling after AngII infusion without high-fat diet treatment. Mechanistic studies indicated that AngII-stimulated macrophages produce urokinase plasminogen activator (uPA) that activates PDGF-D by splicing full-length PDGF-D into the active PDGF-DD. Moreover, bone marrow–specific uPA knockdown decreased active PDGF-DD levels in the heart and improved cardiac remodeling in HFD hypertensive mice. Together, our data provide for the first time a new interaction pattern between macrophage and adipocyte: that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice.
PDGF-D activation by macrophage-derived uPA promotes AngII-induced cardiac remodeling in obese mice
Disclosures: The authors declare no competing interests exist.
C.-C. Ruan’s present address is Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
- Views Icon Views
- Share Icon Share
- Search Site
Yu-Wen Cheng, Ze-Bei Zhang, Bei-Di Lan, Jing-Rong Lin, Xiao-Hui Chen, Ling-Ran Kong, Lian Xu, Cheng-Chao Ruan, Ping-Jin Gao; PDGF-D activation by macrophage-derived uPA promotes AngII-induced cardiac remodeling in obese mice. J Exp Med 6 September 2021; 218 (9): e20210252. doi: https://doi.org/10.1084/jem.20210252
Download citation file: